SIGNIFICANCE OF PIP2 HYDROLYSIS AND REGULATION OF PHOSPHOLIPASE-C ISOZYMES

Phosphatidylinositol 4,5-bisphosphate (PIP2) is an important component of several intracellular signaling pathways. It serves as a substrate for phospholipase C, which produces the second messengers inositol 1,4,5-trisphosphate and diacylglycerol. It is also a substrate for a phosphatidylinositol 3-kinase, and regulates the function of a number of actin-binding proteins. PIP2 has been shown recently to serve as a cofactor for a phosphatidylcholine-specific phospholipase D and as a membrane-attachment site for many signaling proteins containing pleckstrin homology domains. The need to stringently regulate the cellular concentration of PIP2 is reflected in part by the fact that there are at least ten distinct mammalian phospholipase C isozymes and multiple mechanisms linking these isozymes to various receptors.